WHO recommendation and India’s practice on tetanus vaccination—How much is too much?

Introduction

Tetanus is the only non-communicable bacterial, vaccine preventable disease under the National Immunization Schedule (NIS). The causative Clostridium tetani spores are omnipresent around the globe. ¹ The bacterium is anaerobic and produces an endotoxin ² and was discovered in 1884. ³ The disease presents itself mainly in three patterns: following any wound, particularly soiled, in mothers during pregnancy or six weeks afterwards and last in neonates within 28 days of delivery.

In 1989, the World Health Assembly launched its global neonatal tetanus elimination goal, and the Maternal and Neonatal Tetanus Elimination (MNTE) was launched by the World Health Organization (WHO), United Nations Children Fund (UNICEF) and United Nations Population Fund (UNFPA) in 1999. ¹

Tetanus officially becomes a public health problem when the number of neonatal tetanus cases exceeds 1/1000 live births. According to the WHO, 15,103 cases of tetanus have been reported worldwide (7000 in India), of whom 1803 were neonatal (120 in India).^4,5

Vaccination is the most innovative and cost-effective public health intervention protecting against communicable diseases. ⁶ By 2018, 86% of the infants worldwide (116.3 million infants) have received three doses of Diphtheria–Tetanus–Pertussis (DTP3) vaccine. ⁷ The Indian statistic was 88% in 2017. ⁸

NIS recommends three primary dose series of tetanus with Diphtheria and Pertussis (DPT) vaccination and four booster doses given as two DPT and two Td (Tetanus–Diphtheria). The primary dose series are given from the sixth week of birth at an interval of four weeks each. Boosters are given at 18–24 months, 5, 10 and 16 years of age. In total, a child receives seven doses of tetanus toxoid (TT) containing vaccine before adolescence.

During pregnancy, a primigravida pregnant woman receives two doses of Td at four weeks interval mainly to protect against Maternal and Neonatal Tetanus (MNT). If a pregnancy occurs within three years of her last delivery or an abortion during which the mother has been fully immunized, then only a booster dose is given for the current pregnancy. After a trauma, either minor or major, the general practice is to vaccinate the patient with a dose of TT or Td. There is a tendency for giving the vaccine without eliciting a complete history and verifying the documents of the latest vaccination. There is a dire need to reduce this injudicious administration of TT vaccine across all age groups.

According to a WHO position paper on TT/Td immunization of February 2017, a total of six doses of vaccination against tetanus (three primary doses with three boosters) started in childhood and completed in adolescence would provide lifelong immunity. The three TT booster doses should be given at 12–23 months of age, 4–7 years and 9–15 years. Ideally, there should be at least four years between booster doses.

If tetanus vaccination is started during adolescence or adulthood, only five appropriately spaced doses are required to obtain lifelong protection.

Pregnant women and their newborn infants are protected against MNT, if the mother had received six doses (documented by card, vaccination registry and/or history) before reproductive age. Vaccination during pregnancy is recommended only if there is a problem of recall or if adequate documents of vaccination are missing.

Pregnant women who have received only three doses of TT during childhood without booster doses should receive two doses of TT at the earliest opportunity during pregnancy with a minimal interval of four weeks between doses and the second dose at least two weeks before giving birth. To provide lifelong protection, a sixth dose is required at least one year after the fifth dose.

Women who received four TT doses during childhood or pre-adulthood need only one booster dose, which should be given at the first opportunity. To provide lifelong protection, a sixth dose is needed at least one year after the fifth dose.

In case of injuries, if the injury is severe or the patient’s previous tetanus vaccination history is unreliable, then a dose of Td is recommended. A complete five-dose schedule has to be administered for lifelong immunity.

Travelers and health care workers are not at special risk. Hence no separate recommendation is needed.

Implementing WHO recommendations in India

According to the infant schedule, there is one less booster dose as compared to the India NIS. This helps to increase the compliance among parents. The last booster can be a part of school health programme to make sure that all children have completed the schedule, omitting no one (Figure 1). OPEN IN VIEWER

For those who were unvaccinated or incompletely vaccinated till one year of age, the catch-up schedule recommends five doses to provide lifelong immunity (Figure 2). OPEN IN VIEWER

The five-dose schedule of Td vaccine as depicted in Figure 3 (unvaccinated adolescents, adults and pregnant women) for unvaccinated adolescents, adults and pregnant women would provide lifelong immunity. Additional dose is not required after trauma or during a subsequent pregnancy or delivery. Since MNT has been eliminated in India, this schedule would also protect the neonate against neonatal tetanus. OPEN IN VIEWER

Those women who have received three primary doses of DTPCV will need an additional three doses of Td to protect themselves lifelong (Figure 4), while those who have received four doses of childhood DTPCV will need two doses of Td to achieve lifelong immunity (Figure 5). OPEN IN VIEWER

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Figure 5.

Schedule for four doses incomplete vaccination.

Immunogenicity and effectiveness of the vaccine

Using in vivo neutralization tests or modified enzyme-linked immunosorbent assays (ELISA), concentrations >0.01 IU/ml or antibody concentrations of 0.1–0.2 IU/ml are usually considered protective. In children, a three-dose primary series of DTP induce a satisfactory antibody titre. ⁹ Data from serological studies suggest that a primary series of three TTCV doses in infancy plus a booster during the second year of life will provide three to five years of protection. A further booster dose (e.g. in early childhood) will provide protection into adolescence, and another booster during adolescence will induce immunity that lasts through much of adulthood, thus protecting women through their childbearing years.

In the Netherlands, results from use of a six-dose schedule of TTCVs in childhood with the last dose at eight years of age demonstrated that tetanus immunity persisted for at least 20 years after the sixth dose, with a geometric mean titer (GMT) of 0.44 IU/ml in individuals aged 30–34 years. ¹⁰ In adults not previously vaccinated, a third dose, 6–12 months after the first two doses, induces production of high levels of long-lasting tetanus-specific antibodies. Ten years after Tdap or Td booster, tetanus antibody levels still exceeded pre-immunization levels and remained protective ( ≥ 0.10 IU/ml) in ≥ 97% of adolescents and adults. In a study in pregnant women with no previous tetanus vaccination, 78% of those who received two doses during pregnancy had tetanus-specific antibody levels above the protective threshold three years later.

Recommendations

Prevention is the only way to reduce the incidence and subsequent mortality due to tetanus. Vaccine coverage has to be improved and emphasized on completion of the schedule. ¹¹

Complete immunization of infants and children with three primary and three booster doses of TCV.

Conclusion

Tetanus immunization is to protect from the disease and not to improve immunity against it. Hence the recommended WHO schedule should be abided by and the changes incorporated in the India NIS. Treating physicians should elicit a thorough history of prior vaccination before administering an extra dose of TT vaccine. Frequent and irrational administration of TT vaccine after any degree of trauma must be discontinued. Further, misconception about TT vaccination and fear of tetanus disease among the public will be diminished through appropriate hospital practice.